Questions for a New Class of Cholesterol Drugs

By KATIE THOMAS

November 14, 2013

New guidelines governing the use of cholesterol-lowering medicines are a huge change for doctors and a vast number of patients, but the impact on the drug industry is expected to be less tumultuous.

The products that stand to gain the most from the new advice, statin drugs, are mostly sold as inexpensive generics and bring in relatively little revenue for the major pharmaceutical companies. Brand-name drugs that don’t fare as well in the guidelines, like Zetia by Merck and Vytorin, were already viewed with skepticism.

“From a Wall Street perspective, we don’t pay any attention anymore to statins,” said Mark Schoenebaum, a pharmaceutical analyst for the ISI Group. The focus instead, he said, “is on the next generation of still-unapproved drugs.”

It is those drugs — a promising new class of cholesterol-lowering drugs known as PCSK9 inhibitors — whose fate is most thrown into question by the new guidelines, released Tuesday by the two major heart associations. The recommendations place less emphasis on lowering cholesterol to a target level and do not advise using existing drugs other than statins to do so. The PCSK9 inhibitors, which are complex biological drugs that will be injected, have been shown in early trials to significantly lower cholesterol levels, but longer studies have not been completed showing that they reduce the risk of heart disease and death.

The guidelines will not determine whether the Food and Drug Administration approves these new drugs, but they could damp sales if they discourage physicians from prescribing them and insurance companies from paying for them.

Statin drugs are mostly sold as inexpensive generics.

Bill Gallery / Watson Pharmaceuticals, via Associated Press

“The question becomes, what happens in the medical community?” said C. Anthony Butler, an analyst for Barclays. Insurers could balk at reimbursing the cost of the drugs — or make patients contribute more — if they concluded that the guidelines from leading medical authorities did not favor their use.

Leonard S. Schleifer, the chief executive of Regeneron Pharmaceuticals, which is developing such a drug in partnership with Sanofi, said he did not think the new guidelines would delay approval, which the company is hoping will occur in 2015.

He said the company’s understanding was that the F.D.A. would be willing to approve PCSK9 inhibitors based on their ability to lower cholesterol, providing that outcomes studies were already well underway and there were no safety problems. “We don’t believe anything in any of these guidelines changes that basic understanding,” Dr. Schleifer said.

Regeneron, as well as Pfizer and Amgen, which are developing competing drugs, have begun enrolling patients in cardiovascular outcomes trials, but the results are not expected until later in the decade.

Shares of Regeneron rose more than 4 percent Thursday after Bloomberg News reported that an F.D.A. official said that cardiovascular outcomes trials would not need to be completed before the agency would approve such drugs. An F.D.A. spokeswoman said Thursday that the agency would evaluate the drugs based on existing measures like whether they lowered cholesterol levels and blood pressure, in addition to their overall safety profile.

Supporters of the PCSK9 inhibitors said there was a need for new treatments. “Even the most powerful statins have not cured the disease,” said Dr. Jean-Claude Tardif, the director of the Research Centre at the Montreal Heart Institute and a primary investigator for the Pfizer PCSK9 inhibitor. “So we know there is a need for new drugs that are going to hopefully improve the fate of our patients with cardiovascular disease.”

There are more than 25 million prescriptions for Crestor, the statin by AstraZeneca.

Statins are among the most commonly used prescription drugs, and most are sold generically at low prices. One exception is Crestor, a statin made by the British company AstraZeneca, which brought in more than $5.1 billion in sales in 2012 with more than 25 million prescriptions, according to IMS Health, the health research firm.

But while some speculated that doctors might turn more often to Crestor, a powerful statin, because the advice suggests prescribing moderate- or high-intensity statins to patients who are seen to be at particular risk, others said any resulting sales increase was likely to be modest. Crestor is set to lose its patent protection in 2016, so its life span is limited.

Zetia lowers cholesterol in a different way than statins and has not been shown to reduce the risk of heart disease and death, so analysts have long viewed its potential as limited. Merck is awaiting the results of a long-term cardiovascular outcomes trial of Zetia, which are expected next year.

“That will settle all of this,” Dr. Schoenebaum said. If the study shows the drug does not reduce the risk of heart disease and death, its sales will most likely dwindle, he said. If it shows it does reduce risk, “then the guidelines presumably would recommend it,” he said.

In 2012, Zetia brought in $2.6 billion and Vytorin, which combines Zetia with a statin, $1.8 billion, according to company filings.

A spokeswoman for Merck said she did not anticipate a significant business impact because of the guidelines. “We continue to see strong need for our products in the market,” said Pamela Eisele, the Merck spokeswoman. She also noted that the guidelines said physicians “may consider” nonstatin cholesterol-lowing drugs when patients did not respond to statins or could not tolerate them.